Universal or Specific? A Modeling-Based Comparison of Broad-Spectrum Influenza Vaccines against Conventional, Strain-Matched Vaccines

摘要

Despite the availability of vaccines, influenza remains a major public health challenge. A keyreason is the virus capacity for immune escape: ongoing evolution allows the continual circulation of seasonal influenza, while novel influenza viruses invade the human population tocause a pandemic every few decades. Current vaccines have to be updated continually tokeep up to date with this antigenic change, but emerging ‘universal’ vaccines—targetingmore conserved components of the influenza virus—offer the potential to act across allinfluenza A strains and subtypes. Influenza vaccination programmes around the world aresteadily increasing in their population coverage. In future, how might intensive, routineimmunization with novel vaccines compare against similar mass programmes utilizing conventional vaccines? Specifically, how might novel and conventional vaccines compare, interms of cumulative incidence and rates of antigenic evolution of seasonal influenza? Whatare their potential implications for the impact of pandemic emergence? Here we present anew mathematical model, capturing both transmission dynamics and antigenic evolutionof influenza in a simple framework, to explore these questions. We find that, even whenmatched by per-dose efficacy, universal vaccines could dampen population-level transmission over several seasons to a greater extent than conventional vaccines. Moreover, by lowering opportunities for cross-protective immunity in the population, conventional vaccinescould allow the increased spread of a novel pandemic strain. Conversely, universal vaccinescould mitigate both seasonal and pandemic spread. However, where it is not possible tomaintain annual, intensive vaccination coverage, the duration and breadth of immunityraised by universal vaccines are critical determinants of their performance relative to conventional vaccines. In future, conventional and novel vaccines are likely to play complementary roles in vaccination strategies against influenza: in this context, our results suggestimportant characteristics to monitor during the clinical development of emerging vaccinetechnologies.